title: BK virus-associated infection in cerebrospinal fluid of neurological patients and mutation analysis of the complete VP1 gene in different patient groups.
abstract: While BK virus (BKV) is frequently associated with pathological conditions in bone marrow and renal transplant recipients, BKV infection in neurological individuals has been rarely reported. As a result of a BKV, JCV, and SV40 large T antigen-specific multiplex PCR on 2,062 cerebrospinal fluid (CSF) samples from neurological patients suspicious of JCV infection, we identified 20 subjects with at least 1 CSF specimen positive for BKV large T antigen DNA. Because VP1 protein has been suggested to influence the biological/pathological properties of BKV, we tried to sequence the entire VP1 gene in the BKV-positive neurological patients and succeeded in 14 of the 20 neurological patients. To compare the VP1 sequence of the BKV neurological strains with that of non-neurotropic strains in other clinical situations, full-length VP1 DNA was sequenced in 15 renal and 6 bone marrow transplant recipients positive to BKV-viremia, and in 8 pregnant women as non-pathological controls. An increased (respectively, decreased) tendency for mutations in the BC loop (respectively, EF loop) was observed, and no mutations were detected in the CD, GH, and HI loops. Subtype I was predominant (93%) and compared to archetypal BKV (WW), amino acid substitutions were detected in 4/14 neurological patients, 10/15 renal transplant recipients, 3/6 bone marrow transplant patients, and in all the pregnant women. Each patient group had distinctive VP1 mutations, but these unique substitutions were not present in all patients of this group. However, molecular modeling simulations of the VP1 mutants predicted changes in protein surface properties which might affect the VP1-receptor interaction.
authors.affiliation: Host-Microbe Interaction Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Ana
authors.initials: A
authors.lastname: Bárcena-Panero
authors.forename: Marijke
authors.initials: M
authors.lastname: Van Ghelue
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.forename: Juan E
authors.initials: JE
authors.lastname: Echevarría
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fedele
authors.forename: Ugo
authors.initials: U
authors.lastname: Moens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001739:BK Virus / Q000235:genetics; D036022:Capsid Proteins / Q000235:genetics*; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D060885:Multiplex Polymerase Chain Reaction; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000134:cerebrospinal fluid / Q000150:complications / Q000235:genetics*; D011247:Pregnancy; D014412:Tumor Virus Infections / Q000134:cerebrospinal fluid / Q000150:complications / Q000235:genetics*; D055815:Young Adult
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus